The present invention relates to novel chelated 1,8-naphthyridine derivatives and a process for preparing the chelated 1,8-naphthyridine derivatives and 1,8-naphthyridine derivatives. More particularly the invention relates to chelated 1,8-naphthyridine derivatives having the following general formula [I]: ##STR4## wherein X and Y are independently a lower alkyl group, and a process for preparing the chelated 1,8-naphthyridine derivatives [I] and 1,8-naphthyridine derivatives having the following general formula [III]: ##STR5## wherein X and Y are as defined above, from compounds as the starting materials having the following general formula [II]: ##STR6## wherein X and Y are as defined above and R is a lower alkyl group.
The 1,8-naphthyridine derivatives of the general formula [III] are substances useful as pharmaceuticals. Particularly a compound of the general formula [III] wherein X is methyl group and Y is ethyl group is a useful antibacterial substance which is described in the Japanese Pharmacopoeia as nalidixic acid.
There are known various processes for preparing nalidixic acid, i.e. 1-ethyl-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid.
U.S. Pat. No. 3,590,036 discloses a process for preparing nalidixic acid by ethylating a compound (A) with ethyl iodide and hydrolyzing the resulting compound (B) as shown in the following scheme. ##STR7## However, according to this process, the yield of the compound (B) is only 27% by mole as described in Example 16 of the Patent.
U.S. Pat. No. 3,590,036 also discloses a process for preparing nalidixic acid by ethylating a compound (C) with ethyl iodide or diethyl sulfate as shown in the following scheme. ##STR8## In case of conducting the ethylation with expensive ethyl iodide, even if expensive ethyl iodide is employed in large excess, e.g. in an amount of 3.1 times the stoichiometric quantity, the yield of nalidixic acid is 56% by mole. Even if the reaction is conducted in an excessive manner, for instance, even if the reaction is conducted for 5 days under reflux by employing a larger excess of ethyl iodide, i.e. in an amount of 6.1 times the stoichiometric quantity, the yield is at most 66% by mole. In case of conducting the ethylation with diethyl sulfate, not only the process is dangerous due to the toxicity of the ethylating agent, but also the yield is at most 48% by mole.
In U.S. Pat. No. 3,813,406, there is disclosed a process in which nalidixic acid is directly prepared by ring-closing condensation of, in the presence of polyphosphoric acid, a compound of the following formula: ##STR9##